3,7-Inter-m-phenylene-3-oxa-13,14-didehydro-11-deoxy-17-phenyl-4,5,6,18,19,20-hexanor-PGE1 compounds

ABSTRACT

This invention comprises certain analogs of the prostaglandins in which the double bond between C-13 and C-14 is replaced by a triple bond. Also provided in this invention, are novel chemical processes and novel chemical intermediates useful in the preparation of the above prostaglandin analogs. These prostaglandin analogs exhibit prostaglandin-like activity, and are accordingly useful for the same pharmacological purposes as the prostaglandins. Among these purposes are blood pressure lowering, labor induction at term, reproductive-cycle regulation, gastric antisecretory action, and the like.

The present application is a divisional application of Serial No.657,740, filed February 13, 1976, now pending issuance as a UnitedStates Patent.

The present invention relates to prostaglandin analogs, for which theessential material constituting disclosure therefor is incorporated byreference here from Ser. No. 820,974, filed Aug. 1, 1977, which is adivisional application of Ser. No. 657,740.

I claim:
 1. A prostaglandin analog of the formula ##STR1## wherein D is##STR2## wherein Z₄ is ##STR3## WHEREIN G IS 1, 2, OR 3; WHEREIN R₇ is##STR4## WHEREIN Z₃ is oxa or methylene, s is 0, 1, 2, or 3, and T ischloro, fluoro, trifluoromethyl, alkyl of 1 to 3 carbon atoms,inclusive, or alkoxy of 1 to 3 carbon atoms, inclusive, the various T'sbeing the same or different, with the proviso that not more than two T'sare other than alkyl;Wherein L₁ is ##STR5## or a mixture of ##STR6##wherein R₃ and R₄ are hydrogen, methyl, or fluoro, being the same ordifferent, with the proviso that one of R₃ and R₄ is methyl only whenthe other is hydrogen or methyl, with the further proviso that one orboth of R₃ and R₄ is fluoro only when Z₃ is methylene; Wherein M₁ is##STR7## wherein R₅ and R₆ are hydrogen or methyl, with the proviso thatone of R₅ and R₆ is methyl only when the other is hydrogen; andwhereinR₁ is hydrogen, alkyl of 1 to 12 carbon atoms, inclusive, cycloalkyl of3 to 10 carbon atoms, inclusive, aralkyl of 7 to 12 carbon atoms,inclusive, phenyl, phenyl substituted with 1, 2, or 3 chloro or alkyl of1 to 3 carbon atoms, inclusive, or a pharmacologically acceptablecation.
 2. A compound according to claim 1, wherein D is ##STR8##
 3. Acompound according to claim 2, wherein M₁ is ##STR9##
 4. A compoundaccording to claim 3, wherein g is
 1. 5. A compound according to claim4, wherein R₃, R₄, R₅, and R₆ are all hydrogen. 6.15-epi-3,7-inter-m-Phenylene-3-oxa-13,14-didehydro-8β,12α-11-deoxy-17-phenyl-3,4,5,18,19,20-hexanor-PGE₁, methyl ester, a compound according to claim
 4. 7. A compound accordingto claim 2, wherein M₁ is ##STR10##
 8. A compound according to claim 7,wherein g is
 3. 9. A compound according to claim 7, wherein g is
 1. 10.A compound according to claim 9, wherein R₃ and R₄ are both hydrogen.11. A compound according to claim 10, wherein R₅ is methyl. 12.3,7-inter-m-Phenylene-3-oxa-15-methyl-13,14-didehydro-8.beta.,12α-11-deoxy-17-phenyl-4,5,6,18,19,20-hexanor-PGE₁, a compound according to claim
 11. 13.3,7-inter-m-Phenylene-3-oxa-15-methyl-13,14-didehydro-8β,12α-11-deoxy-17-phenyl-4,5,6,18,19,20-hexanor-PGE₁,methyl ester, a compound according to claim
 11. 14. A compound accordingto claim 10, wherein R₆ is methyl. 15.3,7-inter-m-Phenylene-3-oxa-13,14-didehydro-8β,12.alpha.-11-deoxy-17-phenyl-4,5,6,18,19,20-hexanor-PGE₁,15-methyl ether a compound according to claim
 14. 16.3,7-inter-m-Phenylene-3-oxa-13,14-didehydro-8β,12α-11-deoxy-17-phenyl-4,5,6,18,19,20-hexanor-PGE₁,methyl ester, 15-methyl ether, a compound according to claim
 14. 17. Acompound according to claim 10, wherein R₅ and R₆ are both hydrogen. 18.3,7-inter-m-Phenylene-3-oxa-13,14-didehydro-8β,12α-11-deoxy-17-phenyl-4,5,6,18,19,20-hexanor-PGE₁,a compound according to claim
 17. 19.3,7-inter-m-Phenylene-3-oxa-13,14-didehydro-8β,12α-11-deoxy-17-phenyl-4,5,6,18,19,20-hexanor-PGE₁,methyl ester, a compound according to claim
 17. 20. A compound accordingto claim 19, wherein at least one of R₃ and R₄ is methyl.
 21. A compoundaccording to claim 20, wherein R₃ and R₄ are both methyl.
 22. A compoundaccording to claim 21, wherein R₅ is methyl. 23.3,7-inter-m-Phenylene-3-oxa-15,16,16-trimethyl-13,14-didehydro-8β,12α-11-deoxy-17-phenyl-4,5,6,18,19,20-hexanor-PGE₁,methyl ester, a compound according to claim
 22. 24. A compound accordingto claim 21, wherein R₆ is methyl. 25.3,7-inter-m-Phenylene-3-oxa-16,16-dimethyl-13,14-didehydro-8β,12α-11-deoxy-17-phenyl-4,5,6,18,19,20-hexanor-PGE₁,methyl ester, 15-methyl ether, a compound according to claim
 24. 26. Acompound according to claim 21, wherein R₅ and R₆ are both hydrogen. 27.3,7-inter-m-Phenylene-3-oxa-16,16-dimethyl-13,14-didehydro-8β,12α-11-deoxy-17-phenyl-4,5,6,18,19,20-hexanor-PGE₁,a compound according to claim
 26. 28.3,7-inter-m-Phenylene-3-oxa-16,16-dimethyl-13,14-didehydro-8β,12α-11-deoxy-17-phenyl-4,5,6,18,19,20-hexanor-PGE₁,methyl ester, a compound according to claim
 26. 29. A compound accordingto claim 9, wherein at least one of R₃ and R₄ is fluoro.
 30. A compoundaccording to claim 29, wherein R₃ and R₄ are both fluoro.
 31. A compoundaccording to claim 30, wherein R₅ is methyl. 32.3,7-inter-m-Phenylene-3-oxa-15-methyl-16,16-difluoro-13,14-didehydro-8β,12α-11-deoxy-17-phenyl-4,5,6,18,19,20-hexanor-PGE.sub.1,methyl ester, a compound according to claim
 31. 33. A compound accordingto claim 30, wherein R₆ is methyl. 34.3,7-inter-m-Phenylene-3-oxa-15-methyl-16,16-difluoro-13,14-didehydro-8β,12α-11-deoxy-17-phenyl-4,5,6,18,19,20-hexanor-PGE.sub.1,methyl ester, 15-methyl ether, a compound according to claim
 33. 35. Acompound according to claim 30, wherein R₅ and R₆ are both hydrogen. 36.3,7-inter-m-Phenylene-3-oxa-16,16-difluoro-13,14-didehydro-8β,12α-11-deoxy-17-phenyl-4,5,6,18,19,20-hexanor-PGE₁,a compound according to claim
 35. 37.3,7-inter-m-Phenylene-3-oxa-16,16-difluoro-13,14-didehydro-8β,12α-11-deoxy-17-phenyl-4,5,6,18,19,20-hexanor-PGE₁,methyl ester, a compound according to claim
 35. 38. A compound accordingto claim 1, wherein D is ##STR11##
 39. A compound according to claim 38,wherein M₁ is ##STR12##
 40. A compound according to claim 39, wherein gis
 1. 41. A compound according to claim 40, wherein R₃, R₄, R₅, and R₆are all hydrogen. 42.15-epi-3,7-inter-m-Phenylene-3-oxa-13,14-didehydro-11-deoxy-17-phenyl-4,5,6,18,19,20-hexanor-PGE.sub.1,methyl ester, a compound according to claim
 41. 43. A compound accordingto claim 38, wherein M₁ is ##STR13##
 44. A compound according to claim43, wherein g is
 3. 45. A compound according to claim 43, wherein gis
 1. 46. A compound according to claim 45, wherein R₃ and R₄ are bothhydrogen.
 47. A compound according to claim 46, wherein R₅ is methyl.48.3,7-inter-m-Phenylene-3-oxa-15-methyl-13,14-didehydro-11-deoxy-17-phenyl-4,5,6,18,19,20-hexanor-PGE₁,a compound according to claim
 47. 49.3,7-inter-m-Phenylene-3-oxa-15-methyl-13,14-didehydro-11-deoxy-17-phenyl-4,5,6,18,19,20-hexanor-PGE₁,methyl ester, a compound according to claim
 47. 50. A compound accordingto claim 46, wherein R₆ is methyl. 51.3,7-inter-m-Phenylene-3-oxa-13,14-didehydro-11-deoxy-17-phenyl-4,5,6,18,19,20-hexanor-PGE₁,15-methyl ether, a compound according to claim
 50. 52.3,7-inter-m-Phenylene-3-oxa-13,14-didehydro-11-deoxy-17-phenyl-4,5,6,18,19,20-hexanor-PGE₁,methyl ester, 15-methyl ether, a compound according to claim
 50. 53. Acompound according to claim 46, wherein R₅ and R₆ are both hydrogen. 54.3,7-inter-m-Phenylene-3-oxa-13,14-didehydro-11-deoxy-17-phenyl-4,5,6,18,19,20-hexanor-PGE₁,a compound according to claim
 53. 55.3,7-inter-m-Phenylene-3-oxa-13,14-didehydro-11-deoxy-17-phenyl-4,5,6,18,19,20-hexanor-PGE₁,methyl ester, a compound according to claim
 53. 56. A compound accordingto claim 45, wherein at least one of R₃ and R₄ is methyl.
 57. A compoundaccording to claim 56, wherein R₃ and R₄ are both methyl.
 58. A compoundaccording to claim 57, wherein R₅ is methyl. 59.3,7-inter-m-Phenylene-3-oxa-15,16,16-trimethyl-13,14-didehydro-11-deoxy-17-phenyl-4,5,6,18,19,20-hexanor-PGE₁,methyl ester, a compound according to claim
 58. 60. A compound accordingto claim 57, wherein R₆ is methyl. 61.3,7-inter-m-Phenylene-3-oxa-16,16-dimethyl-13,14-didehydro-11-deoxy-17-phenyl-4,5,6,18,19,20-hexanor-PGE₁,methyl ester, 15-methyl ether, a compound according to claim
 60. 62. Acompound according to claim 57, wherein R₅ and R₆ are both hydrogen. 63.3,7-inter-m-Phenylene-3-oxa-16,16-dimethyl-13,14-didehydro-11-deoxy-17-phenyl-4,5,6,18,19,20-hexanor-PGE₁,a compound according to claim
 62. 64.3,7-inter-m-Phenylene-3-oxa-16,16-dimethyl-13,14-didehydro-11-deoxy-17-phenyl-4,5,6,18,19,20-hexanor-PGE₁,methyl ester, a compound according to claim
 62. 65. A compound accordingto claim 45, wherein at least one of R₃ and R₄ is fluoro.
 66. A compoundaccording to claim 65, wherein R₃ and R₄ are both fluoro.
 67. A compoundaccording to claim 66, wherein R₅ is methyl. 68.3,7-inter-m-Phenylene-3-oxa-15-methyl-16,16-difluoro-13,14-didehydro-11-deoxy-17-phenyl-4,5,6,18,19,20-hexanor-PGE₁,methyl ester, a compound according to claim
 67. 69. A compound accordingto claim 66, wherein R₆ is methyl. 70.3,7-inter-m-Phenylene-3-oxa-16,16-difluoro-13,14-didehydro-11-deoxy-17-phenyl-4,5,6,18,19,20-hexanor-PGE₁,methyl ester, 15-methyl ether, a compound according to claim
 69. 71. Acompound according to claim 66, wherein R₅ and R₆ are both hydrogen. 72.3,7-inter-m-Phenylene-3-oxa-16,16-difluoro-13,14-didehydro-11-deoxy-17-phenyl-4,5,6,18,19,20-hexanor-PGE₁,a compound according to claim
 71. 73.3,7-inter-m-Phenylene-3-oxa-16,16-difluoro-13,14-didehydro-11-deoxy-17-phenyl-4,5,6,18,19,20-hexanor-PGE₁,a compound according to claim 71.